Benzocyclopentaindolizines and dibenzindolizines



United States Patent Ofiice 3,336,316 BENZOCYCLOPENTAINDOLIZINES ANDDIBENZINDOLIZINES Richard E. Brown, Hanover, and Robert I. Meltzer,White Meadow Lake, Rockaway, N.J., assignors to Warner- LambertPharmaceutical Company, Morris Plains, N.J., a corporation of DelawareNo Drawing. Original application Apr. 3, 1964, Ser. No. 357,275. Dividedand this application Dec. 8, 1966, Ser. No. 600,038

21 Claims. (Cl. 260-286) This is a divisional application of ourcopending application Ser. No. 357,275, filed Apr. 3, 1964.

This invention relates to a new and novel class of heterocycliccompounds. More particularly, this invention relates to novelsubstituted indolizines of the formula:

41-01 or R and R taken together with the carbon atom to which they areattached represent a keto radical such as or a cyclic ketal radical suchas c Hg) and n may be 1 01' 2.

The symbols R R R R R R and n as used hereinafter have the same meaningas defined.

This invention also includes within its scope a novel process for theproduction of these compounds.

The compounds of this invention contain a fused tetracyclic ring systemin which a substituted aromatic ring A is fused to the 7-8 face ofindolizine nucleus of the formula 3,336,316 Patented Aug. 15, 1967 Thenumbering of the fused ring system is indicated below Exemplary of suchindolizines are:

2,3,3a,5,6,10b,1 1,11a-octahydro-8-methoxy-1H-benzo- [g] cyclopenta [b]indolizine 2,3,3a,5,6,10b,11,1la-octahydro-S-methoxy-lla-rnethyllH-benzo [g] cyclopenta [b] indolizine2,3,3a,5,6,10b,11,11a-octahydro-8-9-dimethoxy-11amethyl-l-carbethoxy-cyclopenta[b] indolizine 2,3,3a,5,6,10b,1 1,1 1a-octahydro-S-hydroxy-1H-benzo- [g]cyclopenta [b] indolizine 2, 3,3-a,5,6,10b,11,1la-octahydro-S-hydroxy-lla-methyl- 1H benzo [g]cyclopenta [b] indolizine 2, 3,3a,5,6,10b,1l,1la-octahydro-8-hydroxy-lla-methyl- I-carboxy-lH-benzo [g] cyclopenta [b] indolizine2,3,3a,5,6,10b,11,1 la-octahydro-S-methoxy-l la-methyllH-benzo [g]cyclopenta [b] indolizine-l-one 2,3,3a,5, 6,10b, 1 1,11a-oct'ahydro-8-hydroxy-1 la-methyllH-benzo [g] cyclopenta [b]indolizine-Lone 1,2,3,4,4a, 6,7, 1 1b,12,12a-decahydro-9-methoxydi=benz[b,g] indolizine 1,2,3 ,4,4a,6,7,11b,12,12a-decahydro-9-methoxy-12amethyl-dibenz [big] indolizine1,2,3,4,4a,6,7,1 lb, 12,12a-decahydro-9-IO-dimethoxy-12a-methyl-l-carbethoxy-dibenz [b,g] indolizine 1,2,3,4,4a,6,7,11b,12,12a-decahydro-9-hydroxy-dibenz [b,g] indolizine 1,2,3,4,4a,-6,7, 11b,12,12a-decahydro-9hydroxy-12amethyl-dibenz [b,g] indolizine1,2,3,4,4a,6,7,1113,12,12a-decahydro-9=hydroxy-12amethyl-l-carboxy-dibenz[b,g] indolizine 1,2,3,4,4a,6,7,1 1b,12a-decahydro-9-methoxy-12amethyl-dibenz [b,g] indolizine-Lone 1,2,3,4,4a,6,7, 1 1b,12,12a-decahyd-ro-9-hydroxy-12amethyl-dibenz [b,g]indolizine-l-one The new and novel compounds of this invention resemblethe steroids structurally and can be considered as C-nor-8-azasteroidsand as such exhibit significant steroidal like properties. Theseproperties include, for example, estrogenic, anabolic, and so on, andare, therefore, useful in the treatment of various endocrine disorders.They also exhibit other pharmacological properties, not-ably on thecardiovascular system such as hypotensive effects in a mammalian hostsuch as mice, dogs and the like. In order to use these compounds ashypotensive agents they are combined with standard pharmaceuticalcarriers such as lactose, dicalcium, phosphate, mannitol and the like toform dosage forms suitable for oral administration such as tablets ordispersible powders. They may also be combined with water or a vegetableoil to form dosage forms suitable for intramuscular or intravenousinjections. In these dosage forms they are generally formulated at aconcentration of about 0.1% to 1% by weight. A dosage regimen of about0.1 mg. to 100 mg. several times daily is required to produce thedesired hypotensive effect. In addition, they are importantintermediates toward the preparation of other substituted indolizinecompounds. Thus, for example, ring A wherein R is hydrogen and R ismethoxy may be reduced employing alkali metals such as sodium -in thepresence of an alcohol such as ethanol in liquid ammonia to give, afterhydrolysis with a dilute mineral acid such as hydrochloric, a compoundof the formula:

OH )jCECH 2)n R1 N H III We have found that compounds of this inventionmay be produced according to the following reaction sequence. Thepreparation of an intermediate lactam of the formula:

is accomplished by either of two methods. In the first method,substituted B-phenethylamines of the formula:

and cycloalkanone-Z-acetic acids or the corresponding esters of theformula:

COOY in which Y may be hydrogen, lower alkyl such as methyl,

ethyl, or propyl; or aralkyl such as benzyl are reacted in equivalentquantities in a high boiling inert solvent such as xylene or toluene.Under such conditions, there is formed an unsaturated lactam of theFormula V below:

Such an intermediate can be catalytically reduced as describedsubsequently to give a saturated lactam such as ILI Exemplary of suchindolizines are:

1,2,5 ,6,1 1,1 la-hexahydro-8-methoxy-1 1a methyl-l-oxobenzo [g]cyclopenta [b] indolizinium perchlorate2,3,6,7,12,l2a-hexahydro-9-methoxy l2a-methyl-1-oxolH-dibenz [b,g]indolizinium perchlorate 1,2,5,6,l1,1la-hexahydr-o 8 methoxylla-methyl-lcarbethoxy-benzo [g] cyclophenta [b] indoliziniumperchlorate 2,3,6,7,12,12a hexahydro 9methoxy-l2a-methyl-lcarbethoxy-lH-dibenz [b,g] indolizinium perchlorateand the like.

Agents which may be employed to effect this cyclization include, forexample, phosphorous oxychloride and the like. Reduction of indolizinessuch as V1 with gaseous hydrogen in the presence of a catalyst such aspalladium on carbon or complex alkali metal hydrides such as sodium orpotassium borohydrides yield the desired saturated indolizines of thisinvention. Alternatively the lactam V may be catalytically reduced withgaseous hydrogen in the presence of palladium on carbon or othersuitable hydrogenation catalyst to form a saturated lactam correspondingto the Formula IV. Such lactams may then be cyclized to give asubstituted indolizine of the structure I Rn R1 N/ J VII Exemplary ofindolizines such as VII are:

1,2,3,3a,5,6,11,11a-octahydro-S-methoxybenzo [g] cyclopenta [b]indolizinium bromide 1,2,3,3a,5,6,11,11a-octahydro-8-methoxy 11amethylbenzo [g] cyclopenta [b] indolizinium bromide 1,2,3,3a,5,6,11,11aoctahydr-o-8-methoxy-1 la-methyl- 1- carbethoxy-benzo [g] cyclopenta [b]indolizinium bromide 1,2,3,3a,5,6,11,11a o-ctahydro 8 hydroxy-benzo [g]icyclophenta [b] indolizinium bromide1,2,3,3a,5,6,11,1la-octahydro-S-hydroxy 11a methylbenzo [g] cyclopenta[b] indolizinium bromide 1,2,3,3a,5,6,11,1la-octahydro 8hydroxy-lla-methyl- '2,3,4,4a,6,7,12,12a-octahydro 9hydroxy-12a-methyllH-dibenz [b,g] indolizinium bromide I2,3,4,4a,6,7,12,12a octahydro-9-hydroxy-12a-methyl-1- carboxy-lH-dibenz[b,g] indolizinium bromide 2,3,4,4a,6,7,12,12aoctahydro 9methoxy-l-oxo-IH- 12a-methyl-dibenz [b,g] indoliziniurn bromide2,3,4,4a,6,7,l2,12a octahydro 9 hydroxy-l-oxo-lH- 12a-methyl-dibenz[b,g] indolizinium bromide and the like.

These indolizines may then be further reduced to compounds whichcorrespond to structural Formula I. Such reduction reactions may hecarried out by employing any one of the reduction methods such as theuse .of gaseous hydrogen in the presence of a catalyst such as palladiumon carbon or of complex alkali metal hydrides such as sodiumborohydride.

The reaction sequence when carried out according to the above proceduresleads predominantly to one of the two possible configurations about the(3-D ring fusion. By employing the following alternate condensationmethod we can obtain both of these steric configurations about this ringjunction thereby giving two isomers. In this second procedure, thestarting substituted B-phenethylamine and cycloalkanone-Z-acetic acid orester are subjected to a reductive condensation carried out in asuitable solvent, such as methanol, ethanol or isopropanol over ahydrogenation catalyst such as palladium on carbon. Under these reactionconditions, there is formed a mixture of two isomeric amino acids ifcycloalkanone-Z-acetic acid is one of the starting materials or twoisomeric amino esters if the corresponding ester is employed as thestarting material. The isomeric amino acids correspond to the formula:

a Hooo HOOC H N IN I N Rr- H R1- H H and H VIII IX Exemplary of suchamino acids are:

6 cis and transZ-methyl-Z-carboxymethyl-3-keto-N-(mmethoxyphenethy-l)-cyclohexylamineand the like.

These isomeric amino acids may be readily separated by taking advantageof the fact that the cis isomer undergoes cyclization to give theearlier-described saturated lactam IV, under much milder conditions thanoccurs with the trans isomer. Thus, for example, in some cases, the cisisomer actually cyclizes to the lactam spontaneously during thereductive condensation step. 'In those cases in which a mixture of theamino acids is obtained from the reductive condensation, it is usuallysufficient to merely dissolve the amino acid mixture by heating in aninert solvent such as acetonitrile or isopropanol to bring about thecyclization of the cis amino acid. The trans amino acid IX is recoveredin pure form by cooling the solution and filtering, and the cis compoundcan then be obtained pure in the lactam form by concentrating thesolution to dryness and washing the residue with water to removeresidual traces of trans amino acid.

The pure cis lactam and trans amino acid can then be cyclized in theusual way with an appropriate cyclization reagent, such as phosphorousoxychloride, to afford the two isomeric substituted i-ndolizinescorresponding to structure VII. Alternatively, the pure trans amino acidmay be-conver-ted to the trans lactam corresponding to structure IV byheating to its melting point, and this product then cyclized to theindolizine corresponding to structure VII.

These indolizines may exist in the form of the quaternary salt VII, ormay be converted to the free base by treatment of the quaternary saltwith an aqueous alkali such as sodium hydroxide, ammonium hydroxide andthe like. Such free bases have the Formula X:

R1 H ti z) n Exemplary of indolizines such as X are:

2, 3,3a,5,6,11a-hexahydro=8-methoxy-1H-benzo[g]cyclopent [b] indolizine1,2,3,4,4 a,6t7,'12aoctahydro-9-methoxy-dibenz [b,g] indolizine2,3,3ia,5,6, 1 La-hexahydro-8-methoxy-l-oxo-1 la-methyl- 1H-benzo[ g]cyclopent [b] indolizine 1,12,3,4,4a,6,7,1Za-octahydro-9-methoxy-1-oxo12amethyl-dibenz [b,g] indolizine2,3,3 a, 5,-6,1*1a-hexahydro-8-methoxy-1-carbethoxy-11amethyllH-benzo[g] cyclopent [b] indolizine1,2,-3,4,4a,-6,7,12a-ootahydro-9-methoxy-l-carbethoxy- IZa-methyldibenz[b, g] indolizine and the like.

The following examples are given in order to further illustrate thepresent invention. All temperatures given are in the centigrade scale.

EXAMPLE 1 Cis and trans-Z-carboxymethyl-N-(m-meth0xyphenethyl)cyclohexylamine A mixture of 1.51 grams 10 mmoles) ofm-methoxyphenethylamine, 1.56 grams (10 mmoles) ofcyclohexanone-2-acetic acid, 0.5 gram of 10% palladium on charcoalcatalyst and SOml. of ethanol is hydrogenated at ambient temperature and50 psi. pressure until hydrogen absorption is complete (ca 16 hours).The catalyst is filtered, and the solvent removed by vacuumdistillation. The white solid residue is Wa-rmed with 50 ml.isopropanol, cooled, diluted with a little ether and filtered afiter onehour to give pure cis2car-boxymethyl-N-(mmethoxy-phenethyl)-cyclohexylamine as whitecrystals, M.P. 133-4 which may be recrystallized from water. Thefiltrate is concentrated to dryness and the white solid residue istriturated with water and filtered to give another small amount of thecis acid. The filtrate is concentrated to dryness and tritu-rated withacetone to give pure trans 2-carboxymethyl-N-(m-methoxyphenethyl)-cyclohexylamine as white crystals, M.P.134-5". Thin layer chromatography using silica gel as the stationaryphase and a 75-25 mixture of methanol-acetone as the moving phase(iodine as developing agent) shows the cis and trans amino acids assharp spots of Rf=0.4 and 0.5, respectively.

EXAMPLE 2 Cis-Z,3,4,4a,6,7,12,12a-ctahydro-9-meth0xy-1H-dibenz[b,g]indolizinium bromide A slurry of 7.4 grams of cisZ-carbOXymethyl-N-(mmethoxyphenethyl)-cyclohexylamine in 300 ml. benzenecontaining 50 ml. of phosphorous oxychloride is refluxed for two hours.The mixture is concentrated under reduced pressure to a yellow oil. Theoil is dissolved in 200 ml. of water, chopped ice is added, and themixture is made basic with sodium hydroxide solution. The precipitatedoil is extracted with ether. The ether is dried over magnesium sulfate,and dry hydrogen bromide is passed in. The precipitated yellow oilcrystallizes on rubbing with isopropanol. The yellow solid isrecrystallized from isopropanol to give cis-2,3,4,4a,6,7,12,l2a-octahydro-9- methoxy-1H-dibenz[b,g]indolizinium bromide asyellow crystals, M.P. 175-8. The quaternary perchlorate can be preparedby treating the bromide with dilute perchloric acid, and melts at 11618after recrystallization from ethanol.

The quaternary salt can be dissolved in water and made basic by additionof dilute alkali to give a precipitate of the free base,cis-1,2,3,4,4a,6,7,l2a-octahydro-9- methoxy-dibenz[b,g]indolizine as ayellow oil.

EXAMPLE 3 T rans-2,3,4,4a,6, 7 ,1 2,1 2a-octahydro-9-methoxy-1 Hdibenz[b,g]indolizinium perchlorate In the same way as described inExample 2, 3.0 grams of trans-hexahydro1-(m-methoxyphenethyl)-2-indolinone in a mixture of 150 ml. of benzeneand 30 ml. of phosphorous oxychloride are cyclized to give trans-2,3,4,4a,6,7,12,12a-ootahydro 9-methoxy 1H-dibenz[b,g]indoliziniumperchlorate, as white plates, M.P. 182-3 after recrystallization fromethanol.

The free base, trans-1,2,3,4,4a,6,7,12a-octahydro-9-methoxydibenz[b,g]indolizine is obtained as white crystals, M.P. 92-4",in the same way as described in Example 2.

EXAMPLE 4 T rails-2,3 ,4,4a,6, 7 ,1 2,1 2 a-0ctahydr0-9-hydr0xy-1 Hdibenz[b,g]indolizinium bromide A solution of 2.7 grams oftrans-2,3,4,4a,6,7,12,12aoctahydro 9-methoxy lH-dibenz[b,g]indoliziniumperchlorate in ml. of acetone is poured into 200 ml. of 5% sodiumhydroxide solution. The precipitated solid is extracted with 2 portionsof 25 ml. each of 48% hydrobromic acid, and the combined hydrobromicacid solutions are refluxed for 6 hours. This solution is concentratedto dryness under reduced pressure and the oily residue is crystallizedby rubbing with isopropanol. The crude solid is filtered andrecrystallized from n-propanol to givetrans-2,3,4,4a,6,7,12,12a-octahydro-9-hydroxy-lH-dibenz[b,g]indoliziniumbromide, as a white powder, M.P. 269-71".

8 EXAMPLE 5 Cis-2,3,4,4a,6,7,12,12a-0ctahydr0-9-hydr0xy-IH-dibenz[b,g]ind0lizinium bromide A solution of 5.0 grams ofcis-2,3,4,4a,6,7,12,12a-octahydro-9-methoxy-1H-dibenz[b,-g]indoliziniumbromide in ml. of 48% hydrobromic acid is refluxed for 6 hours. Thesolution is concentrated to a solid which is recrystallized frommethanol to give cis-2,3,4,4a,6,7,12,12a-octahydro-9-hydroxylH-dibenz[b, g] indolizinium bromide as white crystals, M.P. 277-9 EXAMPLE 6Trans 2-carb0xymethyl-N-(m-methoxyphenethyl)cyclopentylamine andcis-3,3a,4,5,6,6a-hexahydro l-(mmethoxyphenethyl)cyclopenta[b]pyrr0l-2-(1H) -one In the same way as described in Example1, 7.55 grams of m-methoxyphenethylamine and 7.10 grams ofcyclopentanone-Z-acetic acid are subjected to reductive condensation in200 ml. ethanol over 1.0 gram 10% palladium on carbon catalyst. Thewhite residue from removal of the catalyst and solvent is slurried in300 ml. of acetonitrile and the mixture refluxed with stirring for 15minutes. It is cooled and filtered to givetrans-Z-carboxymethyl-N-(m-methoxyphenethyl)-cyclopentylamine as a purewhite solid, M.P. 194-5 The acetonitrile filtrate is concentrated to anoil. The oil is dissolved in ether, and the ether washed with a 5%solution of sodium bicarbonate, dried over magnesium sulfate andconcentrated to give cis-3,3a,4,5,6,6a-hexahydro-l-(mmethoxyphenethyl)cyclopenta[b]pyrrol 2- (1H)-one as an oil.

EXAMPLE 7 Cis-1,2,3,3a,5,6,11,11a-0ctahydr0-8-mezh0xybenz0[g]cyclopent[b] indolizinium bromide In the same way as described inExample 2, 4.3 grams of cis-3,3a,4,5,6,6a-hexahydr0-1(m-methoxyphenethyl) cyclopenta[b]pyrrol-2-(1H)-one are cyclized with 15ml. of phosphorous oxychloride in ml. of benzene to giveeis-1,2,3,3a,5,6,11,11a octahydro 8 methoxybenzo[g]cyclopent[b]indolizinium bromide as a yellow oil. The quaternaryperchlorate is prepared from the bromide, and melts at 121-5 afterrecrystallization from isopropanol. The free basecis-2,3,3a,5,6,1la-hexahydro 8 methoxy-1H-benzo[g]cyclopenta[b]indollzine is obtained from the salt asdescribed in Example 4, and is a yellow oil.

EXAMPLE 8 Trans-1,2,3,3a,5,6,11,11a-octahydr0-8-meth0xybenz0[g]cycl0pent[b]indolizinium perchlorate A solution of 0.5 gram oftrans-Z-carboxymethyl-N- (m-methoxyphenethyl)cyclopentylamine in 10 ml.of phosphorous oxychloride is held at 100? for 2 hours, then evaporatedto dryness. The oily residue is dissolved in water and 10% perchloricacid is added until precipitation is complete. The pale yellow solid isfiltered to give trans- 1,2,3,3a,5,6,11,11a-octahydro-8methoxybenzo[g]cyclopent[b] indolizinium perchlorate as white needles,M.P. 172-4 after recrystallization from ethanol. The free base, trans2,3,3a,5,6,11,11a hexahydro 8 methoxy 1H- benzo[g]cyclopent[b]indolizineis obtained from the salt as described in Example 2 and is a whitesolid, M.P. 613.

EXAMPLE 9 Trans-1,2,3,3a,5,6,11,11a-0ctahydr0-8-hydr0xybenzo [g]cycl0pent[b] indolizinium bromide In the same way as described inExample 6, a solution of 5.0 grams of trans 1,2,3,3a,5,6,11,11aoctahydro 8- methoxybenzo g] cyclopent [b indolizinium perchlorate isdemethylated with 100 ml. of hydrobromic acid to givetrans-1,2,3,3a,5,6,11,11a-octahydro 8 hydroxybenzo[g]cyclopent[b]indolizinium perchlorate, M.P. 300 after recrystallizationfrom ethanol.

EXAMPLE 10 Cis-1,2,3,3a,5,6,11,1Ia-ctahydr0-8-hydr0xybenz0 [g]cyclopenta[b] indolizinium bromide In the same way as described inExample 6, 4.8 grams of cis-1,2,3,3a,5,6,l1,11a-octahydro-8 methoxybenzo[g] cyclopent[b]indolizinium perchlorate is demethylated with 100 ml. of48% hydrobromic acid to give cis-1,2,3, 3a,5,6,11,lla-octahydro 8hydroxybenzo[g]cyclopenta [b]indolizinium bromide as white crystals,M.P. 2456 after recrystallization from acetonitrile.

EXAMPLE 11 2,3,3a,5,6,10b,11,11a-octahydro-8-methoxy-JH-benzo [g]cyclopenta[b] indolizine hydrobromide A solution of 0.5 gram oftrans-1,2,3,3a,5,6,11,11aoctahydro 8methoxybenzo[g]cyclopent[b]indolizinium perchlorate in 50 ml. ofmethanol is treated with 1.0 gram of potassium borohydride. The mixtureis left for 1 hour at ambient temperature, then evaporated to dryness.The residue is partitioned between ether and water. The ether phase isdried over magnesium sulfate and dry hydrogen bromide passed in. Theprecipitate is filtered to give 2,3,3a,5,6,10b,11,11a-octahydro-8methoxy 1H- benzo[g]cyclopenta[b]indolizine hydrobromide as a whitesolid, M.P. 196-9".

It is to 'be understood that the foregoing detailed description is givenmerely by way of illustration and that many variations may be madetherein Without departing from the spirit of our invention.

Having described our invention, what we desire to secure by LettersPatent is:

1. A compound selected from the group consisting of the stereoisomersand mixtures thereof of compounds represented by the formulas:

wherein R and R each is a member selected from the group consisting ofhydrogen, hydroxy, and lower alkoxy;

R is a member selected from the group consisting of hydrogen and loweralkyl; and R and R are each hydrogen. 2. The compound of claim 1 whichis 1,2,3,3a,5,6,11,

10 11a octahydro 8 methoxybenzo[g] cyclopent[b]indoliziinium bromide.

3. The compound of claim 1 which is 1,2,3,3a,5,6,11,lla-octahydro-S-methoxy 11a methyl benzo[g]cyclopent[b]indoliziniumbromide.

4. The compound of claim 1 which is 1,2,3,3a,5,6,11, Ila-octahydro 8methoxy 11a methyl l carbethoXy-benzo[g]cyclopent[b]indoliziniumbromide.

5. The compound of claim 1 which is 1,2,3,3a,5,6,ll, Ila-octahydro 8hydroxy benzo[g] cyclopent[b]indolizinium bromide.

6. The compound of claim 1 which is 1,2,3,3a,5,6,11, 11a octahydro 8hydroxy 11a methyl benzo[g] cyclopenta[b]indolizinium bromide.

'7. The compound of claim 1 which is 1,2,3,3a,5,6,11, Ila-octahydro 8hydroxy 11a methyl l carboxybenzo [g] cyclopenta [b] indoliziniumbromide.

8. The compound of claim 1 which is 1,2,3,3a,5,6,1l, Ila-octahydro 8methoxy 11a methyl 1 oxobenzo [g] cyclopenta[b] indolizinium bromide.

9. The compound of claim 1 which is 1,2,3,3a,5,6,11, Ila-octahydro 8hydroxy 11a methyl 1 oxobenzo [g] cyclopent[b]indolizinium bromide.

10. The compound of claim 1 which is 2,3,4,4a,6,7,12, 12a-octahydro 9methoxy 1H dibenz[b,g]indolizinium bromide.

11. The compound of claim 1 which is 2,3,4,4a,6,7,12, 12a-octahydro 9,10dimethoxy 12a methyl 1H dibenz[b,g]indolizinium bromide.

12. The compound of claim 1 which is 2,3,4,4a,6,7,l2, 12a-octahydro 9methoxy 12a methyl 1 carbethoxy-lH-di-benz[b,g] indolizinium bromide.

13. The compound of claim 1 which is 2,3,4,4a,6,7,12, 12a-octahydro 9hydroxy 1H dibenz[b,g]indolizinium bromide.

14. The compound of claim 1 which is 2,3,4,4a,6,7,12, 12a-octahydro 9hydroxy 12a methyl 1H dibenz [b,g] indolizinium bromide.

15. The compound of claim 1 which is 2,3,4,4a,6,7,12, 12a-octahydro 9hydroxy 12a methyl carboxy 1H- dibenz[b,g]indolizinium bromide.

16. The compound of claim 1 which is 2,3,4,4a,6,7,12, 12a-octahydro 9methoxy 1 0x0 1H 12a methyldibenz[-b,g]indolizinium bromide.

17. The compound of claim 1 which is 2,3,4,4a,6,7,12, 12a-octahydro 9hydroxy 1 oxo 1H 12a methyldibenz[b,g]indolizinium bromide.

18. The compound of claim 1 which is l,2,5,6,11, 11ahexahydro 8 methoxy11a methyl 1 oxobenzo[g] cyclopenta [b]indolizinium perchlorate.

19. The compound of claim 1 which is 2,3,6,7,12,12ahexahydro 9 methoxy12a methyl 1 0x0 1H dibenz [-b,g] indolizinium perchlorate.

2.0. The compound of claim 1 which is 1,2,5,6,11, 11ahexahydro 8 methoxy11a methyl 1 carbethoXy-,

benzo[ g] cyclopenta[b]indolizinium perchlorate.

21. The compound of claim 1 which is 2,3,6,7,12,12ahexahydro 9 methoxy12a methyl 1 carbethoxylH-dibenz[b,g]indolizinium perchlorate.

No references cited.

ALEX MAZEL, Primary Examiner.

D. DAUS, Assistant Examiner.

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF THE STEREOISOMERSAND MIXTURES THEREOF COMPOUNDS REPRESENTED BY THE FORMULAS: